Aminoglycoside antibiotics (AGs) are important for the treatment of a variety of serious infectious diseases including septicemia, complicated intra-abdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. AGs are the mainstay of treating Pseudomonas infection in patients with cystic fibrosis and one of the best classes of medication for treating multiple drug resistant TB throughout the world. AGs would be even more widely used today if it were not for the fact that as many as 20% of patients treated with AGs develop measurable irreversible hearing loss and a significant fraction of these people become functionally deaf. This side effect, called ototoxicity, has moved aminoglycoside antibiotics from what would otherwise be a cheap and effective therapy into a treatment of last resort. Previously, we identified a class of small molecular compounds that were effective at preventing hair cell death in the zebrafish and later showed them to also protect hearing and prevent inner ear hair cell death in rats exposed to high doses of AGs. Our Phase I SBIR grant enabled us to show that these compounds did not interfere with the bactericidal properties of AGs and have a wide margin of safety in a variety of standard in vitro safety tests. The Phase I work led to the selection of our leading clinical candidate. This Phase II project seeks to continue to advance our candidate through the required steps of GLP/GMP manufacturing of a medicine and through the rigorous safety testing dictated by the FDA for in-human trials. We have assembled a team of hearing experts, medicinal chemists, pharmacologists, infectious disease experts, toxicologists and regulatory experts to guide the project through FDA IND application and approval. The project will result in the first medicine ever approved by the FDA to prevent hearing loss of any type.